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In this study, we conducted a thorough investigation into the mechanisms by which miR-29 influences lipid metabolism. Thirty-two cows were selected and categorized into distinct groups based on their liver triglyceride (TG) content: healthy, mild fatty liver, and moderate fatty liver groups. Dairy cows with moderate fatty liver showed higher levels of hepatic lipid accumulation, MDA content and serum AST, ALT and ALP contents and lower hepatic catalase CAT and SOD activities. Subsequently, hepatocytes isolated from healthy calves were exposed to sodium oleate (SO) in the presence or absence of pre-incubation with miR-29 inhibitor or inhibitor NC. Pre-transfection with miR-29 inhibitor resulted in reduced hepatocyte lipid accumulation and MDA levels, as well as decreased levels of AST, ALT, and ALP in the supernatant. In the miR-29 inhibitor + SO group, there was an increase in the expression of SREBP-1 , FAS , SCD1 , and Sirt1 . Meanwhile, the expression of PPARα , CPT1 , CPT2 , PGC-1α , NRF-1 , UCP2 , and miR-29 were observed to be decreased. In comparison to the miR-29 inhibitor + SO group, some of the measured indicators showed partial reversal in the miR-29 inhibitor + siSirt1 + SO group. Collectively, these findings provide evidence that miR-29 may play a crucial role in the pathogenesis of fatty liver in dairy cows.

Cellulases play an important role in the bioconversion of lignocellulose. Microorganisms found in extreme environments are a potentially rich source of cellulases with unique properties. Due to the uniqueness of the environment, the abundant microbial resources in the Qinghai-Tibet Plateau (QTP) are worth being explored. The aim of this study was to isolate and characterize an acidic, mesophilic cellulase-producing microorganism from QTP. Moreover, the fermentation conditions for cellulase production were optimized for future application of cellulase in the development of lignocellulose biomass. A novel cellulase-producing strain, Penicillium oxalicum XC10, was isolated from the soil of QTP. The cellulase produced by XC10 was a mesophilic cellulase that exhibited good acid resistance and some cold-adaptation properties, with maximum activity at pH 4.0 and 40°C. Cellulase activity was significantly enhanced by Na + (p < 0.05) and inhibited by Mg 2+ , Ca 2+ , Cu 2+ , and Fe 3+ (p < 0.05). After optimization, maximum cellulase activity (8.56 U/mL) was increased nearly 10-fold. Optimal fermentation conditions included an inoculum size of 3% (v/v) in a mixture of corn straw (40 g/L), peptone (5 g/L), and Mg 2+ (4 g/L), at pH 4.0, 33°C, and shaking at 200 rpm. The specific properties of the P. oxalicum XC10 cellulase suggest the enzyme may serve as an excellent candidate for the bioconversion and utilization of lignocellulose biomass generated as agricultural and food-processing wastes., (© 2024 International Union of Biochemistry and Molecular Biology, Inc.)

Zinc oxide nanoparticles (nano-ZnO) have diverse applications in numerous biomedical processes. The present study explored the effects of these nanoparticles on antioxidation, inflammation, tight junction integrity, and apoptosis in heat-stressed bovine intestinal epithelial cells (BIECs). Primary BIECs that were isolated and cultured from calves either were subjected to heat stress alone (42°C for 6 h) or were simultaneously heat-stressed and treated with nano-ZnO (0.8 μg/mL). Cell viability, apoptosis, and expression of genes involved in antioxidation (Nrf2, HO-1, SOD1, and GCLM), inflammation-related genes (TLR4, NF-κB, TNF-α, IL-6, IL-8, and IL-10), intestinal barrier genes (Claudin, Occludin, and ZO-1), and apoptosis-related genes (Cyt-c, Caspase-3, and Caspase-9) were assessed to evaluate the effect of nano-ZnO on heat-stressed BIECs. The nanoparticles significantly increased cell viability and decreased the rate of apoptosis of BIECs induced by heat stress. In addition, nano-ZnO promoted the expression of antioxidant-related genes HO-1 and GCLM and anti-inflammatory cytokine gene IL-10, and inhibited the pro-inflammatory cytokine-related genes IL-6 and IL-8. The nanoparticles also enhanced expression of the Claudin and ZO-1 genes, and decreased expression of the apoptosis-related genes Cyt-c and Caspase-3. These results reveal that nano-ZnO improve the antioxidant and immune capacity of BIECs and mitigate apoptosis of intestinal epithelial cells induced by heat stress. Thus, nano-ZnO have potential for detrimental the adverse effects of heat stress in dairy cows., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Probiotics are the most promising alternative to antibiotics for improving animal production and controlling pathogenic infections, while strains derived from natural hosts are considered highly desirable due to their good adaptation to the gastrointestinal tract. The aim of this study was to screen Lactobacillus with broad-spectrum antibacterial activity from broilers fed an antibiotic-free diet and evaluate their potential as poultry probiotics. A total of 44 lactic acid bacteria (LAB) strains were isolated from the intestines of healthy broilers, among which 3 strains exhibited outstanding antimicrobial activity and were subsequently identified through 16S rRNA sequencing as Enterococcus faecium L8, Lactiplantibacillus plantarum L10, and Limosilactobacillus reuteri H11. These three isolates demonstrated potent bacteriostatic activity against Staphylococcus aureus , Listeria monocytogenes , Escherichia coli , and Salmonella cholerae , with inhibition zones ranging from 15.67 ± 1.53 to 21.33 ± 0.58 mm. The selected LAB strains exhibited high tolerance to acid and bile salts, with L. reuteri H11 displaying the highest survival rate (ranging from 34.68% to 110.28%) after exposure to 0.3% ( w / v ) bile salts for 6 h or a low pH environment (pH 2, 2.5, and 3) for 3 h. Notably, L. reuteri H11 outperformed other strains in terms of hydrophobicity (84.31%), auto-aggregation (53.12%), and co-aggregation with E. coli ATCC 25922 (36.81%) and S. aureus ATCC 6538 (40.20%). In addition, the three LAB isolates were either fully or moderately susceptible to the tested antibiotics, except for strain L8, which resisted gentamycin and vancomycin. Consequently, these three LAB strains, especially L. reuteri H11, isolated from the intestines of broiler chickens, represent promising probiotic candidates that can be employed as feed additives to enhance production performance and control poultry pathogens.

Ischemia/reperfusion (I/R)-induced neural damage and neuroinflammation have been associated with pathological progression during stroke. Netrin-1 is an important member of the family of laminin-related secreted proteins, which plays an important role in governing axon elongation. However, it is unknown whether Netrin-1 possesses a beneficial role in stroke. Here, we employed the middle cerebral artery occlusion (MCAO) model to study the function of Netrin-1 in alleviating brain injuries. Our results demonstrate that Netrin-1 rescued poststroke neurological deficits and inhibited production of the inflammatory cytokines such as interleukin 6 (IL-6) and endothelial chemokine (C-X-C motif) ligand 1 (Cxcl1). Importantly, Netrin-1 protected against MCAO-induced dysfunction of the blood-brain barrier (BBB) in mice and a reduction in the expression of the tight junction (TJ) protein occludin. Additionally, we report that Netrin-1 could ameliorate oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury and prevent aggravation in endothelial monolayer permeability in bEnd.3 human brain microvascular endothelial cells (HBMVECs). Mechanistically, Netrin-1 ameliorated OGD/R-induced decrease in occludin and Kruppel-like factor 2 (KLF2) in HBMVECs. Notably, silencing of KLF2 abolished the beneficial effects of Netrin-1 in protecting endothelial permeability and occludin expression, suggesting that these effects are mediated by KLF2. In conclusion, our findings suggest that Netrin-1 could constitute a novel therapeutic strategy for ischemic stroke., (© 2024 Wiley Periodicals LLC.)

Objective: This study aimed to investigate the effect of dietary guanidinoacetic acid (GAA) on the growth performance, slaughter traits, myofiber, and adenine nucleotide of meat-type rabbits., Methods: Experimental treatments consisted of control (CON) and GAA addition at 0.04% (T1), 0.08% (T2), and 0.12% (T3) of diet. A total of 240 weaned rabbits (meat-type male Chinese black rabbits) were randomly distributed into four groups with six replicates of ten rabbits each., Results: Results showed that the three doses of GAA increased (p<0.05) final body weight, carcass weight, the density and area of quadriceps femoris fiber; and T3 showed significant effects (p<0.05) on weight gain, feed/gain, and dressing percentage, and the traits of longissimus fiber, compared to CON. Dietary GAA increased (p<0.05) the meat color a* and b* in longissimus and quadriceps; and T3 showed the lowest (p<0.05) shear force of longissimus. Furthermore, GAA increased (p<0.05) the contents of adenosine triphosphate and total adenine nucleotide in longissimus and quadriceps. In longissimus adenosine triphosphate, total adenine nucleotide, and adenylate energy charges, T3 treatment was most effective (p<0.05); while T2 and T3 treatment was more effective (p<0.05) than T1 in quadriceps. Additionally, linear or quadratic responses (p<0.05) to the increased doses of GAA were found on body weight gain, meat color, total adenine nucleotide, and adenylate energy charges., Conclusion: It is concluded that GAA can be used in the rabbit diet to improve growth and carcass traits, and these are related to the high levels of muscle adenine nucleotide.

Heat stress (HS) has a negative impact on the health and performance of dairy cows, resulting in economic losses. Damage to the intestinal epithelium is the main cause of the adverse effects of heat stress on bovine health. This study investigated the repair capability of L -arginine ( L -Arg) in reducing the adverse effects of HS on bovine intestinal epithelial cells (BIECs). BIECs were treated as follows: (1) control cells were cultured at 37 °C continuously and received no L -Arg; (2) cells in HS group were grown at 42 °C for 6 h followed by 12 h at 37 °C; and (3) the L -Arg group was cultured at 42 °C for 6 h, then treated with L -Arg at 37 °C for 12 h. HS disrupted redox homeostasis and reduced viability in BIECs, while treatment with L -Arg (6 mmol/L) for 12 h markedly reduced the negative effects of HS. L -Arg protected cells by preventing HS-induced changes in mitochondrial membrane-potential, inflammation, apoptosis-related gene expression and regulation of antioxidant enzymes. The above results indicated that L -Arg reduced the level of damage from HS in BIECs by lowering oxidant stress and inflammation, suggesting that L -Arg could be an effective dietary addition to protect cows from adverse intestinal effects caused by HS.

Background: Scores for predicting the long-term mortality of severe pneumonia are lacking. The purpose of this study is to use machine learning methods to develop new pneumonia scores to predict the 1-year mortality and hospital mortality of pneumonia patients on admission to the intensive care unit (ICU)., Methods: The study population was screened from the MIMIC-IV and eICU databases. The main outcomes evaluated were 1-year mortality and hospital mortality in the MIMIC-IV database and hospital mortality in the eICU database. From the full data set, we separated patients diagnosed with community-acquired pneumonia (CAP) and ventilator-associated pneumonia (VAP) for subgroup analysis. We used common shallow machine learning algorithms, including logistic regression, decision tree, random forest, multilayer perceptron and XGBoost., Results: The full data set of the MIMIC-IV database contained 4697 patients, while that of the eICU database contained 13760 patients. We defined a new pneumonia score, the "Integrated CCI-APS", using a multivariate logistic regression model including six variables: metastatic solid tumor, Charlson Comorbidity Index, readmission, congestive heart failure, age, and Acute Physiology Score III. The area under the curve (AUC) and accuracy of the integrated CCI-APS were assessed in three data sets (full, CAP, and VAP) using both the test set derived from the MIMIC-IV database and the external validation set derived from the eICU database. The AUC value ranges in predicting 1-year and hospital mortality were 0.784-0.797 and 0.691-0.780, respectively, and the corresponding accuracy ranges were 0.723-0.725 and 0.641-0.718, respectively., Conclusions: The main contribution of this study was a benchmark for using machine learning models to build pneumonia scores. Based on the idea of integrated learning, we propose a new integrated CCI-APS score for severe pneumonia. In the prediction of 1-year mortality and hospital mortality, our new pneumonia score outperformed the existing score., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Idiopathic pulmonary haemosiderosis is a rare disease primarily affecting children. The condition is characterized by widespread bleeding from alveolar capillaries, resulting in symptoms such as haemoptysis, shortness of breath and iron deficiency anaemia. However, it is not a specific disease and sometimes can manifest solely as anaemia, which may be easily overlooked and misdiagnosed. The purpose of this case report was to describe a 1-year-old boy who exhibited haemolytic anaemia as the only symptom of idiopathic pulmonary haemosiderosis, with the intention of offering clinical insights into the precise diagnosis and subsequent management of this rare and easily misdiagnosed disease. Clinicians should keep idiopathic pulmonary haemosiderosis in mind when evaluating children with haemolytic anaemia and promptly initiate testing and treatment to prevent misdiagnosis and improve outcomes., Competing Interests: Declaration of conflicting interestsThe authors declare that there are no conflicts of interest.

This study was conducted to evaluate the effects of dietary supplementation with Glycyrrhiza polysaccharide (GCP) on growth performance, serum biochemistry, immunity, and egg laying in female quail. 300 1-day-old female quail were sorted into four dietary treatments with five replicate cages of 15 birds each. The basic diet in the four treatment groups was supplemented with 0, 500, 1000 and 1500 mg/kg GCP, and the experiment continued for 80 days. Results showed that dietary supplementation with GCP significantly ( p  < 0.05) increased average daily gain in a dose-dependent fashion, and decreased ( p  < 0.05) the feed-to-gain ratio and mortality. The relative weights of the thymus and bursa of Fabricius increased ( p  < 0.05) linearly with increasing dose of GCP from 0 to 1500 mg/kg on day 20. GCP birds showed higher serum levels of protein, glucose, immunoglobulin A and immunoglobulin M, but lower serum triglycerides ( p  < 0.05) on day 50. GCP increased ( p  < 0.05) average laying rate and average egg weight linearly from days 60 to 80, whereas feed to egg ratio was decreased ( p  < 0.05). Taken together, these results revealed that GCP could improve growth performance, serum biochemistry, immunity, and egg laying in female quail. Therefore, GCP may be a potential replacement for antibiotic growth promoters in poultry.

Fatty liver (i.e., hepatic lipidosis) is a prevalent metabolic disorder in dairy cows during the transition period, characterized by excess hepatic accumulation of triglyceride (TG), tissue dysfunction, and cell death. Detailed pathological changes, particularly hepatic fibrosis, during fatty liver remain to be determined. Liver fibrosis occurs as a consequence of liver damage, resulting from the excessive accumulation of extracellular matrix, which distorts the architecture of the normal liver, compromising its normal synthetic and metabolic functions. Thus, we aimed to investigate liver fibrosis status and its potential causal factors including oxidative stress, hepatocyte apoptosis, and production of inflammatory cytokines in the liver of cows with fatty liver. Forty-five dairy cows (parity, 3-5) were selected, and liver biopsy and blood were collected on the second week postpartum (days in milk, 10-14 d). On the basis of the degree of lipid accumulation in liver, selected cows were categorized into normal (n = 25; TG <1% wet wt), mild fatty liver (n = 15; 1% ≤ TG <5% wet wt), and moderate fatty liver (n = 5; 5% ≤ TG <10% wet wt). Compared with normal cows, blood concentrations of nonesterified fatty acids and β-hydroxybutyrate, along with alanine aminotransferase and aspartate aminotransferase activities, were greater in the cows with fatty liver (mild and moderate). Hepatic extracellular matrix deposition, as indicated by Picrosirius red staining, was greater in cows with fatty liver than those with normal ones. In addition, we observed an increased proportion of collagen type I fiber in extracellular matrix with increased lipid accumulation in the liver. Compared with normal cows, the area of α-smooth muscle actin (α-SMA)-positive staining along with the mRNA abundance of collagen type I α 1 (COL1A1), ACTA2 (gene encoding α-SMA), and transforming growth factor-β (TGFB) were greater in cows with fatty liver. Compared with normal cows, hepatic contents of malondialdehyde, glutathione disulfide, and 8-isoprostane were greater, whereas total antioxidant capacity, the hepatic content of glutathione, and activities of antioxidant indicators, including superoxide dismutase, glutathione peroxidase, and catalase, were lower in cows with fatty liver. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells and abundance of apoptosis-related molecules BAX, CASP3, CASP8, and CASP9 were greater in cows with fatty liver. However, mRNA abundance of the anti-apoptotic gene BCL2 did not differ. The mRNA abundance of pro-inflammatory cytokines including tumor necrosis factor-α (TNFA), interleukin-1β (IL1B), and interleukin-6 (IL6) was greater in the liver of cows with fatty liver. Overall, the present study indicated that fibrosis is a common pathological response to liver damage and is associated with oxidative stress, hepatocyte death, and inflammation., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Objective: The purpose of this study was to characterize real-world studies (RWSs) registered at ClinicalTrials.gov to help investigators better conduct relevant research in clinical practice., Methods: A retrospective analysis of 944 studies was performed on February 28, 2023., Results: A total of 944 studies were included. The included studies involved a total of 48 countries. China was the leading country in terms of the total number of registered studies (37.9%, 358), followed by the United States (19.7%, 186). Regarding intervention type, 42.4% (400) of the studies involved drugs, and only 9.1% (86) of the studies involved devices. Only 8.5% (80) of the studies mentioned both the detailed study design type and data source in the "Brief Summary". A total of 49.4% (466) of studies had a sample size of 500 participants and above. Overall, 63% (595) of the studies were single-center studies. A total of 213 conditions were covered in the included studies. One-third of the studies (32.7%, 309) involved neoplasms (or tumors). China and the United States were very different regarding the study of different conditions., Conclusion: Although the pandemic has provided new opportunities for RWSs, the rigor of scientific research still needs to be emphasized. Special attention needs to be given to the correct and comprehensive description of the study design in the Brief Summary of registered studies, thereby promoting communication and understanding. In addition, deficiencies in ClinicalTrials.gov registration data remain prominent., Competing Interests: All authors declared no potential conflicts of interest in this work., (© 2023 Li et al.)

Dairy calves are highly susceptible to the negative effects of heat stress, which can cause organ hypoxia after blood redistribution, damage the intestinal barrier, and trigger intestinal oxidative stress. This study aimed to investigate the antioxidant effects of monoammonium glycyrrhizinate (MAG) on calf small intestinal epithelial cells under heat stress in vitro. Small intestinal epithelial cells were isolated from a 1-d-old healthy calf and purified by differential enzymatic detachment. The purified cells were divided into seven groups. The control group was cultured with DMEM/F-12 at 37 °C for 6 h, and the treatment groups were cultured with 0, 0.1, 0.25, 0.5, 1, or 5 μg/mL MAG at 42 °C for 6 h. Heat stress causes oxidative damage to cells. Adding MAG to the medium can significantly improve cell activity and reduce cellular oxidative stress. MAG significantly increased the total antioxidant capacity and superoxide dismutase activity caused by heat stress, and significantly decreased malondialdehyde and nitric oxide levels. The MAG treatment also reduced lactate dehydrogenase release, increased mitochondrial membrane potential, and decreased apoptosis under heat stress. MAG also upregulated the expression of the antioxidant-related genes, Nrf2 and GSTT1, in heat-stressed intestinal epithelial cells and significantly downregulated the expression of the heat shock response-related proteins, MAPK, HSP70, HSP90, and HSP27. From the above results, we conclude that 0.25 μg/mL MAG improves the capability of the antioxidant system in small intestinal epithelial cells to eliminate reactive oxygen species by activating antioxidant pathways, improving the oxidant/antioxidant balance, lowering excessive heat shock responses, and reducing intestinal oxidative stress., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Lactic acid bacteria (LAB) as probiotic candidates have various beneficial functions, such as regulating gut microbiota, inhibiting intestinal pathogens, and improving gut immunity. The colonization of the intestine is a prerequisite for probiotic function. Therefore, it is necessary to screen the highly adherent LAB. In this study, the cell surface properties, such as hydrophobicity, auto-aggregation, co-aggregation, and adhesion abilities of the six chicken-derived LAB to Caco-2 cells were investigated. All six strains showed different hydrophobicity (21.18-95.27%), auto-aggregation (13.61-30.17%), co-aggregation with Escherichia coli ATCC 25922 (10.23-36.23%), and Salmonella enterica subsp. enterica serovar Typhimurium ATCC 13311 (11.71-39.35%), and adhesion to Caco-2 cells (8.57-26.37%). Pediococcus pentosaceus 2-5 and Lactobacillus reuteri L-3 were identified as the strains with strong adhesion abilities (26.37% and 21.57%, respectively). Moreover, these strains could survive in a gastric acid environment at pH 2, 3, and 4 for 3 h and in a bile salt environment at 0.1%, 0.2%, and 0.3% ( w / v ) concentration for 6 h. Furthermore, the cell-free supernatant of P. pentosaceus 2-5 and L. reuteri L-3 inhibited the growth of enteropathogenic bacteria and the strains inhibited the adhesion of these pathogens to Caco-2 cells. In this study, these results suggested that P. pentosaceus 2-5 and L. reuteri L-3, isolated from chicken intestines might be good probiotic candidates to be used as feed additives or delivery vehicles of biologically active substances.

This study aimed to evaluate the effects of reducing dietary CP and supplementing rumen protected-methionine (RPM) on production performance, blood parameters, digestibility of nutrients or ruminal fermentation in lactating Holstein dairy cows. A total of 96 lactating cows were randomly assigned to 1 of 2 treatments: a diet containing 17.3% CP without RPM (control group; CON; n = 49) or a diet containing 16.4% CP and supplemented with 15.0 g/d of RPM (treatment group; RPM; n = 47). No effect was observed in the RPM group on milk yield, milk composition and digestibility of nutrients. The results of blood parameters showed that cows in the RPM group exhibited lower blood urea nitrogen concentration than in CON group. Rumen microbial crude protein (MCP) was higher in the RPM group compared to the CON group. Ruminal volatile fatty acid (VFA) concentrations were not different between treatments except for butyrate and isovalerate, which were higher in the RPM group than the CON group 2 h after feeding. In conclusion, reducing dietary CP with RPM supplementation did not limit milk yield, milk composition or digestibility of nutrients, but could improve nitrogen utilization, synthesis of MCP and partially increase VFA production 2 h after feeding cows., Competing Interests: Author YZ was employed by Evonik (China) Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Wei, Dou, Liu, Yan, Li, Khan, Zhang and Xiao.)

In this study we investigated the effect of MAG on fatty deposit-induced degeneration of primary calf hepatocytes induced by sodium oleate. Primary hepatocytes were isolated from dairy calves and cultured before allocation to the following treatment groups: control (untreated), model (starved for 12 h before treatment with 0.25 mM sodium oleate to induce steatosis-like changes, and the MAG group pretreated with MAG (0.1, 0.25, 0.5, and 1.5 mM) for 12 h before sodium oleate treatment (0.25 mM) for 12 h). To evaluate the effect of MAG on fat-induced degradation of primary hepatocytes, we evaluated lipid deposition, cell viability, apoptosis rate, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in the culture supernatant, and expression of oxidant and antioxidant enzymes (LDH, MDA, GSH, and CAT), as well as the expression of lipid metabolism-related genes (PPARα, SREBP-1c, ChREBP, CPT1, CPT2, and MTP) and apoptosis-related genes (Cyt-c, Caspase 9, Caspase 8, Caspase 3, Bax, and Bcl-2). MAG significantly reduced lipid accumulation in hepatocytes induced by sodium oleate (P < 0.05), increased cell viability, decreased the apoptosis rate (P < 0.05), and significantly decreased ALT and AST activity in the culture supernatant (P < 0.05). MAG significantly decreased MDA levels in cells and LDH levels in the culture supernatant, while GSH and CAT levels were increased (P < 0.05). MAG significantly increased the expression of the lipid transport- and metabolism-related genes MTP, PPARα, CPT1 and CPT2, and decreased ChREBP expression (P < 0.05). At concentrations higher than 0.25 mM, MAG significantly decreased SREBP-1c expression (P < 0.05). MAG significantly decreased the expression of the apoptosis-related genes Cyt-c, Caspase 9, Caspase 8, Caspase3 and Bax, while Bcl-2 expression was increased (P < 0.05). These findings demonstrate that MAG improves the antioxidant capacity of hepatocytes and effectively reduces lipid deposition by inhibiting the expression of lipid metabolism- and apoptosis-related genes., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In the current study, we assessed the effects of antibacterial peptide-producing Bacillus subtilis (BS), gallic acid (GA) and cellulase (CL) on the fermentation quality and bacterial community of various varieties of whole-plant corn silage. Three different varieties of whole-plant corn (Yuqing386, Enxiai298, and Nonghe35) were treated with 0.02% BS (fresh material basis), 0.2% GA (fresh material basis) and 0.02% CL (fresh material basis), after which 45 days of anaerobic fermentation were conducted. With the exception of its low dry matter content, the results showed that Yuqing386's crude protein, water-soluble carbohydrate, and lactic acid contents were significantly higher than those of the other two corn varieties. However, its acid detergent fiber and cellulose contents were significantly lower than those of the other two corn varieties. Among the three corn variety silages, Yuqing386 had the highest relative abundance of Lactobacillus at the genus level and the biggest relative abundance of Firmicutes at the phylum level. In addition, the three additives markedly enhanced the quantity of dry matter and crude protein as compared to the control group. The application of GA considerably decreased the level of neutral detergent fiber while significantly increasing the content of lactic acid and water-soluble carbohydrates. Even though all additives enhanced the structure of the bacterial community following silage, the GA group experienced the greatest enhancement. On a phylum and genus level, the GA group contains the highest relative abundance of Firmicutes and Lactobacillus , respectively. Overall, of the three corn varieties, Yuqing386 provides the best silage qualities. GA has the biggest impact among the additions employed in this experiment to enhance the nutritional preservation and fermentation quality of whole-plant corn silage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Wang, Wang, Zhao, Zhang, Jia, Zhai, Zhao and Li.)

Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is an inborn metabolic disorder that affects fatty acid oxidation and the catabolism of branched-chain amino acids, vitamins B and energy metabolism. In this study, the induced pluripotent stem cell (iPSC) line LZUSHi002-A from PBMCs of a 10-year-old male patient with ETFDH mutations using the episomal plasmids was established, which is an ideal in vitro model to understand the exact pathogenesis of MADD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: This study aims to comprehensively evaluate the characteristics of clinical drug trials to facilitate the collection of evidence for COVID-19 drug treatments., Methods: A retrospective analysis of 910 trials retrieved on August 7, 2020., Results: A total of 910 registered clinical trials with at least one drug intervention were evaluated. The number of registrations (32.4%, 295) from the United States accounted for nearly one-third of the total and far exceeded that of other countries individually. Furthermore, the peak number of trials were registered in April (34.3%, 312). Over half of the trials (51.2%, 466) are in the recruitment phase, and only 4.2% (38) of the trials have been completed. The median (interquartile range) estimated enrollment is 127 (59, 365). In 39% (355) of trials, the estimated enrollment is less than 100 participants. A total of 94.5% (790) of the trials use randomization in the allocation, 82.7% (753) use a parallel intervention mode, and 52.2% (475) use masking. A total of 287 drug names have been standardized and mapped. "Hydroxychloroquine" is the leading drug among the registered trials (7.47%, 68). Among the main countries contributing to investigations on "hydroxychloroquine", the United States ranks first with 36.76% (25) of the trials., Conclusion: The designs of COVID-19 clinical drug trials have greatly improved in terms of the implementation of randomization and, particularly, blinding methods. In terms of drug reuse, the number of drug types has greatly increased, and hundreds of drugs have been used for efficacy screening. The emergence of large-sample registration trials is expected to address the uncertainty regarding the current clinical efficacy of some drugs., Competing Interests: All authors declare no potential conflicts of interest in this work., (© 2020 Wang et al.)

Objective: Early recognition of children with severe Hand-Foot-and-Mouth disease (HFMD) is especially important, as severe cases are associated with poor prognosis. To accomplish this, authors designed a quantitative assessment tool to build a nomogram to assist in clinical diagnosis., Methods: A total of 2332 HFMD patients were enrolled in this study; 1750 cases in the mild group and 582 cases in the severe group. Analysis of all of the data was performed using R software version 3.4.3. Multivariate logistic regression was utilized to screen predictors to construct a nomogram model. Finally, predictive performance of the model was evaluated using a receiver operating characteristic (ROC) curve and classifier calibration plot., Results: A nomogram was constructed with five variables: age, peak temperature, fever duration, pathogen, and vomiting. For the nomogram, the area under the curve was 0.87, and the model prediction accuracy rate was 85.2%. Depending upon the comparison of the area under the ROC curve, the nomogram model was superior to the traditional pediatric clinical illness score (PCIS). With the help of the Hosmer-Lemeshow test and resampling model calibration curve, the fitting performance of the nomogram was stable., Conclusions: With advantages such as simplicity, intuitiveness, and practicality, the nomogram (including age, peak temperature, fever duration, pathogen, and vomiting) is capable of predicting severe HFMD and has certain auxiliary value in clinical applications.

The study investigated the impact of feeding OmniGen-AF ® (OG; Phibro Animal Health, Quincy, IL) from dry-off to week 4 of lactation at two doses on production performance and metabolic adaptation of multiparous Holstein cows. Forty-eight cows were blocked and assigned randomly to three treatments: OG was fed at 0 g/head/day (CON), 60 g/head/day (OG60), or 90 g/head/day (OG90). No difference was observed in dry matter intake (DMI) throughout the experiment, whereas feeding OG tended to decrease the percentage body weight change (PWC) on week 2. Although colostrum yield was not affected by treatment, colostrum IgG production of OG90 tended to be higher than that of CON. OG supplementation did not affect overall milking performance but decreased milk SCC during the first 4 weeks of lactation. In prepartum, OG supplementation decreased the concentrations of serum albumin and calcium, and increased serum globulin. OG supplementation tended to increase serum total protein, globulin, and calcium contents postpartum. Furthermore, reduced incidence of mastitis and udder edema were observed. In conclusion, supplementing cows with OG from dry-off period reduces or modulates the inflammation responses associated with parturition, potentially resulting in improved postpartum health, while feeding OG more than 60 g/head/day did not warrant further benefits., (© 2018 Japanese Society of Animal Science.)

The objective of the present study is to determine the effect of phytic acid (PA), sodium oxalate (SO) and sodium silicate (SS) on non-heme iron bioavailability in both the presence and absence of ascorbic acid (AA) using an in vitro digestion/Caco-2 cell model, and the levels of AA needed to promote Fe absorption from Fe complexed with PA, SO or SS were also determined. The results indicated that adding PA at 1:1, 3:1, 5:1 and 10:1 molar as compared to Fe decreased ferrous iron uptake by 55.80 %(P < 0.05), 72.33 % (P < 0.05), 73.32 % (P < 0.05), and 73.26 % (P < 0.05), respectively. Adding SS at 1:1, 3:1, 5:1 and 10:1 molar as compared to Fe also decreased ferrous iron uptake by 51.40 % (P < 0.05), 66.12 %(P < 0.05), 60.19 % (P < 0.05) and 45.11 % (P < 0.05), respectively. Adding SO at 5:1 and 10:1 molar as compared to Fe decreased ferrous iron uptake by 40.81 % (P < 0.05) and 33.14 % (P < 0.05), respectively. When adding AA to iron plus organic acid medias reached molar ratios of 5:5:1 AA:PA:Fe, 3:5:1 AA:SO:Fe and 5:5:1 AA:SS:Fe, iron absorption from FeSO4 were significantly increased (P < 0.05). However, no significant effect was observed in iron absorption from FeCl3 when adding AA to the media. The results showed that PA, SS or SO decreases iron uptake from ferrous Fe, and AA can counteract their inhibiting effect on ferrous iron absorption and thus increase ferrous iron uptake. The results may be important for elucidating factors affecting iron bioavailability in the small intestine and for the development of foods with improved iron bioavailability.